Functional inactivation, of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes
Functional inactivation, of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes
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DOI：
10.1101/gad.908001
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发表时间：
2001-08-01
影响因子：
10.5
通讯作者：
Le Roith, D
中科院分区：
文献类型：
--
作者：
Fernández, AM;Kim, JK;Le Roith, D
外周胰岛素抵抗和胰岛素作用受损是2型糖尿病的主要特征。这种主要疾病的第一个可观察到的缺陷发生在肌肉中，其中响应胰岛素的葡萄糖处置受损。我们已经开发了一种转基因小鼠与显性负性胰岛素样生长因子-I受体（KR-IGF-IR）专门针对骨骼肌。KR-IGE-IR的表达导致突变体与内源性IGF-I和胰岛素受体之间形成杂合受体，从而废除这些受体的正常功能并导致胰岛素抵抗。胰腺P细胞功能障碍在相对较早的年龄发展，导致糖尿病。这些小鼠为研究人类2型糖尿病发展的分子机制提供了极好的模型。
Peripheral insulin resistance and impaired insulin action are the primary characteristics of type 2 diabetes. The first observable defect in this major disorder occurs in muscle, where glucose disposal in response to insulin is impaired. We have developed a transgenic mouse with a dominant-negative insulin-like growth factor-I receptor (KR-IGF-IR) specifically targeted to the skeletal muscle. Expression of KR-IGE-IR resulted in the formation of hybrid receptors between the mutant and the endogenous IGF-I and insulin receptors, thereby abrogating the normal function of these receptors and leading to insulin resistance. Pancreatic P-cell dysfunction developed at a relative early age, resulting in diabetes. These mice provide an excellent model to study the molecular mechanisms underlying the development of human type 2 diabetes.